Prognostic Significance of Actinin-4 Protein Expression and Gene Amplification in Endometrial Carcinoma

J Obstet Gynaecol Res. 2025 Nov;51(11):e70132. doi: 10.1111/jog.70132.

Abstract

Objective: This study aimed to investigate the clinical significance of actinin-4 in endometrial carcinoma. Actinin-4, an actin-binding protein involved in cytoskeletal dynamics, has been implicated in the progression of various cancers; however, its precise role in endometrial carcinoma is not fully understood. This research sought to evaluate actinin-4 protein expression and gene amplification and correlate these findings with clinicopathological parameters and patient survival to determine its prognostic value.

Methods: A retrospective analysis was conducted on endometrial carcinoma patients who underwent surgical resection. Actinin-4 protein expression was assessed using immunohistochemical staining (IHC), and ACTN4 gene amplification was evaluated by fluorescence in situ hybridization (FISH). The intensity of actinin-4 staining was graded, and gene amplification of ACTN4 was defined using the ACTN4/CEP19 ratio. Statistical analysis, including Kaplan-Meier survival analysis and Cox proportional hazards modeling, was performed to correlate actinin-4 expression with clinicopathological features and survival outcomes.

Results: Overexpression of actinin-4 protein by IHC was significantly associated with advanced clinical stage and histological subtypes. While no significant difference was observed in overall survival (OS), patients with high actinin-4 IHC demonstrated significantly poorer progression-free survival (PFS). ACTN4 gene amplification by FISH was significantly associated with poorer prognosis for both OS and PFS compared to the group without amplification.

Conclusion: This study suggests that actinin-4 plays a role in the progression of endometrial carcinoma, particularly influencing tumor aggressiveness and progression-free survival.

Keywords: ACTN4; actinin‐4; endometrial carcinoma; fluorescence in situ hybridization; immunohistochemical staining.

MeSH terms

  • Actinin* / genetics
  • Actinin* / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Endometrial Neoplasms* / diagnosis
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / mortality
  • Endometrial Neoplasms* / pathology
  • Female
  • Gene Amplification*
  • Humans
  • Middle Aged
  • Prognosis
  • Retrospective Studies

Substances

  • Actinin
  • ACTN4 protein, human
  • Biomarkers, Tumor